Knock-down of odr-3 and ife-2 additively extends lifespan and healthspan in C. elegans
Autor: | Dmitri Toren, Simona Ghenea, Vimbai Netsai Charity Samukange, Gabriela Bunu, Robi Tacutu, Ioan Valentin Matei |
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Jazyk: | angličtina |
Rok vydání: | 2021 |
Předmět: |
Aging
ife-2 odr-3 Mutant ved/biology.organism_classification_rank.species Longevity Biology GTP-Binding Protein alpha Subunits Gi-Go medicine.disease_cause synergism medicine Animals Eukaryotic Initiation Factors Model organism Caenorhabditis elegans Caenorhabditis elegans Proteins Mutation Genetic interventions integumentary system ved/biology Effector Wild type RNA-Binding Proteins Forkhead Transcription Factors Cell Biology Cell biology DNA-Binding Proteins genetic interventions Gene Expression Regulation Gene Knockdown Techniques RNA Interference lifespan extension Research Paper |
Zdroj: | Aging (Albany NY) |
ISSN: | 1945-4589 |
Popis: | Genetic manipulations can ameliorate the aging process and extend the lifespan of model organisms. The aim of this research was to identify novel genetic interventions that promote both lifespan and healthspan, by combining the effects of multiple longevity-associated gene inactivations in C. elegans. For this, the individual and combined effects of the odr-3 mutation and of ife-2 and cku-70 knock-downs were studied, both in the wild type and daf-16 mutant backgrounds. We found that besides increasing the lifespan of wild type animals, the knock-down of ife-2 (starting at L4) also extends the lifespan and healthspan of long-lived odr-3 mutants. In the daf-16 background, ife-2 and odr-3 impairment exert opposing effects individually, while the daf-16; odr-3; ife-2 deficient animals show a similar lifespan and healthspan as daf-16, suggesting that the odr-3 and ife-2 effector outcomes converge downstream of DAF-16. By contrast, cku-70 knock-down did not extend the lifespan of single or double odr-3; ife-2 inactivated animals, and was slightly deleterious to healthspan. In conclusion, we report that impairment of odr-3 and ife-2 increases lifespan and healthspan in an additive and synergistic manner, respectively, and that this result is not improved by further knocking-down cku-70. |
Databáze: | OpenAIRE |
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